Anti-dementia drugs could result in harmful weight loss, say researchers

Medications commonly used to treat dementia could result in harmful weight loss, according to UC San Francisco researchers, and clinicians need to account for this risk when prescribing these drugs to older adults, they said.

Their study appears online and in the August issue of the Journal of the American Geriatrics Society.

"This is very relevant to patient care because unintentional weight loss in older adults is associated with many adverse outcomes, including increased rates of institutionalization and mortality, a decline in functional status, and poorer quality of life," said lead author Meera Sheffrin, MD, geriatrics fellow in the UCSF School of Medicine at the UCSF-affiliated San Francisco VA Medical Center. "Our study provides evidence in a large, real-world population that cholinesterase inhibitors may contribute to clinically significant weight loss in a substantial proportion of older adults with dementia."

Alzheimer's disease and other dementias are prevalent, affecting one in six people over age 80. The main drug treatments, a class of medications called cholinesterase inhibitors (i.e., donepezil, galantamine, rivastigmine), are marginally beneficial for most patients and may have serious side effects such as gastrointestinal symptoms.

Weight loss also is a significant problem in dementia patients and linked to increased mortality. Data from randomized controlled trials suggests this weight loss may be an under-recognized side effect of cholinesterase inhibitors, but evidence is limited and conflicting.

In this study, Sheffrin and her colleagues used national VA data from 2007-2010 to evaluate patients age 65 or older diagnosed with dementia who received a new prescription for a cholinesterase inhibitor or other new chronic medication. The primary outcome was timed to a 10-pound weight loss over a 12-month period, as this represents a degree of loss that would be noticed by a clinician and perhaps prompt further action in considering the causes and potential treatments.

A total of 1,188 patients started on cholinesterase inhibitors were matched to 2,189 patients started on other medications. At 12 months, 78 percent were still on the inhibitors, compared to 66 percent for other medications. About 29.3 percent of patients on the inhibitors experienced significant weight loss, compared to 22.8 percent of non-users.

These results demonstrated that patients started on the medications had a higher risk of clinically significant weight loss over a 12-month period compared to matched controls, Sheffrin said. Specifically, one out of every 21 patients treated experienced at least a 10-pound weight loss.

Further research is needed to validate these findings and address study limitations, including if there is a specific subgroup in which starting cholinesterase inhibitors had a higher risk of weight loss, as this study may have been underpowered to find those differences. The sample also included mainly older male veterans, so the generalizability of the findings to women is uncertain, the researchers said.

"Clinicians should take into account the risk of weight loss when weighing the risks and benefits of prescribing cholinesterase inhibitors in patients with dementia," the authors write. "In addition, clinicians should monitor for weight loss if these medications are prescribed and consider discontinuing cholinesterase inhibitors if significant weight loss occurs."